SGS Papers

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The effect of hydroxyquinoline-based gel

on pessary-associated bacterial vaginosis:
a multicenter randomized controlled trial
Kate V. Meriwether, MD; Rebecca G. Rogers, MD; Ellen Craig, CNM; Sean D. Peterson, MS;
Robert E. Gutman, MD; Cheryl B. Iglesia, MD
OBJECTIVE: Pessaries are important options for women with pelvic
floor disorders, but many pessary users experience bacterial vaginosis
(BV). The aim of this study was to evaluate the effect of TrimoSan gel
(Milex Pessaries, Cooper Surgical, Trumbull, CT) on BV prevalence
among pessary users.
STUDY DESIGN: Women presenting for a pessary fitting completed
questionnaires on vaginal symptoms and hormone therapy use and
underwent a BV BLUE test and slide collection for BV analysis by
Nugents criteria. Following pessary fitting, women were randomized
to either standard pessary care with the use of TrimoSan placed
vaginally twice weekly or to standard pessary care without TrimoSan
gel. Women returned 2 weeks and 3 months later for a repeat slide
collection for Gram stain, BV BLUE testing, and completion of questionnaires on vaginal symptoms and desire to continue the pessary.
RESULTS: There were 184 women randomized after successful fitting
(92 to the TrimoSan group), and 147 (79%) presented for 3-month
follow up. Mean age was 56
16 years; patients were mostly white

(57%) or Hispanic (23%), and 36% were using hormone therapy. The
groups did not differ in the prevalence of BV by Nugents criteria at 2
weeks (20% TrimoSan vs 26% no gel, P .46) or 3 months (24%
TrimoSan vs 23% no gel, P .82), nor did they differ in BV by BV BLUE
testing at 2 weeks (0% TrimoSan vs 4% no gel, P .12) or 3 months
(3% TrimoSan vs 0% no gel, P .15). The prevalence of at least one
vaginal symptom did not differ between groups at 2 weeks (44%
TrimoSan vs 45% no gel, P .98) or 3 months (42% TrimoSan
vs 32% no gel, P .30). The TrimoSan group was equally likely to
want to continue their pessary use compared with the standard care
group at 2 weeks (90% vs 86%, P .64) and 3 months (63% vs 60%,
P .76).
CONCLUSION: TrimoSan gel in the first 3 months of pessary use does

not decrease the prevalence of BV or vaginal symptoms and does not

alter the likelihood of a woman desiring to continue pessary use.
Key words: bacterial vaginosis, discharge, pessary, removal,
TrimoSan

Cite this article as: Meriwether KV, Rogers RG, Craig E, et al. The effect of hydroxyquinoline-based gel on pessary-associated bacterial vaginosis: a multicenter
randomized controlled trial. Am J Obstet Gynecol 2015;213:729.e1-9.

elvic oor support disorders are

common and debilitating to
women, resulting in a signicant deterioration in quality of life and overall
health. Pelvic oor disorders are prevalent, with up to 25% of women having
at least one symptomatic pelvic oor

disorder.1 Although surgery for these

disorders is increasingly common,2 many
women cannot undergo surgery or prefer nonsurgical treatment options.
Many women can be successfully tted
with a pessary, a silicone device placed in
the vagina to provide pelvic support for

From the Department of Obstetrics and Gynecology (Drs Meriwether and Rogers and Ms Craig),
University of New Mexico School of Medicine (Mr Peterson), Albuquerque, NM, and Departments of
Obstetrics and Gynecology and Urology, MedStar Washington Hospital Center/Georgetown
University, Washington, DC (Drs Gutman and Iglesia).
Received Dec. 19, 2014; revised April 12, 2015; accepted April 23, 2015.
This study was supported by grant 3A302A from the University of New Mexico Clinical Translational
Science Center and by the MedStar Washington Hospital Center funding for trainee investigator
research.
R.G.R. is a Chair Data Safety Monitoring Board for the Transform trial sponsored by American
Medical Systems and receives royalties from Up-to-Date and McGraw-Hill. The other authors report
no conict of interest.
Presented in oral format at the 41st annual scientic meeting of the Society of Gynecologic Surgeons,
Orlando, FL, March 22-25, 2015.
Corresponding author: Kate Meriwether, MD. meriwet2@salud.unm.edu
0002-9378/$36.00  2015 Elsevier Inc. All rights reserved.  http://dx.doi.org/10.1016/j.ajog.2015.04.032

the treatment of pelvic organ prolapse

and stress urinary incontinence.3 Although pessaries relieve symptoms in the
majority of users, nearly half of women
discontinue pessary use within 1 year
because of a variety of troublesome side
effects,4 including vaginal discharge and
odor. Patients who meet established
goals of pessary use are more likely to
continue the pessary,5 so clinicians are in
need of evidence-based means to maintain pessary satisfaction after tting.
Bacterial vaginosis (BV), a shift in the
ecological balance of the vagina leading
to malodorous vaginal discharge, is
common among pessary users and may
negatively affect their experience with a
pessary. Prior authors have published
that up to 30% of women with a pessary
experience BV, in contrast to 10% in the
general population.6 Many providers
attempt to avoid pessary-related BV by
counseling patients on hygiene measures

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729.e1

SGS Papers
and care, but no randomized trials investigate the care of a pessary after tting.7
TrimoSan gel (Milex Pessaries, Cooper
Surgical, Trumbull, CT), a mildly acidic
vaginal lubricant that is dispensed with
some pessaries, may lower the pH of the
vagina and keep the vaginal ecosystem in
balance during pessary use, but no clinical
trials examine its effect on BV or on other
outcomes.
We conducted a randomized, controlled trial to determine whether TrimoSan gel decreases the prevalence of
BV or bothersome vaginal symptoms
during the rst 3 months of pessary use.
We hypothesized that the TrimoSan gel
would decrease BV and vaginal symptoms compared with women not using
the TrimoSan gel.

M ATERIALS

AND

M ETHODS

This was a multicenter, randomized,

single-blind, controlled trial of patients
who were tted for a pessary for any
indication at 2 tertiary care centers, from
July 1, 2010, through Dec. 31, 2011, at
MedStar Washington Hospital Center
(Washington, DC) and from July 1,
2012, through May 5, 2014, at the University of New Mexico Health Sciences
Center (Albuquerque, NM).
The primary outcome was the determination of BV by Nugents criteria on
Gram stain 3 months after pessary
tting. The study was approved by the
institutional review boards at both clinical sites after ethics committee approval
and was registered at ClinicalTrials.gov
(identier number NCT01471457).
Potential patients were identied
prior to or at the time of a pessary tting
visit, and they were enrolled after
providing written, informed consent.
We approached all patients who were
older than 18 years of age, suitable for
follow-up, and undergoing a pessary
tting for any indication.
Patients were excluded if they were
younger than 18 years of age, had a
known allergic or suspected adverse reaction to TrimoSan gel or any of its
components, had an inability to use a
pessary or TrimoSan as indicated,
already had used a pessary within the last
12 months, had a history of frequent or
chronic BV (>2 episodes per year or

ajog.org
symptoms longer than 6 months of the
last 12 months), had a history of active
vaginal ulcerative disease (active ulcers
from atrophy, herpes, or mesh erosion
with more than 2 episodes of ulcers per
year or last ulcer <1 month ago), were
using long-term antibiotics for indications not listed previously, were
unable to speak English, were unable to
provide informed consent, or were unable to be tted with a pessary.
If patients were randomized at the
time of the initial pessary tting but
unable to retain the pessary or be successfully tted before leaving the ofce
examination and declined a second
attempt at pessary tting, they were
excluded after randomization for failure
to be tted with a pessary. Patients who
were randomized and t with a pessary
who were planning on wearing their
pessary continuously at home and
coming to the ofce for cleaning/
removal were still included in the study.
Patients completed baseline questionnaires on their medical history and
health, use of hormone therapy (HT)
orally and/or vaginally, any vaginal
products or medications being used in
the vagina, and a questionnaire on
vaginal symptoms including vaginal
discharge, shy odor, clear or gray vaginal
discharge, too much vaginal discharge,
vaginal discharge interfering with sex,
vaginal itching, vaginal pain, vaginal pain
interfering with sex, and vaginal sores.
Any HT use (any HT) was dened as
the use of systemic (oral, transdermal, or
vaginal HT), and vaginal hormone
therapy use (vaginal HT) was dened as
any hormone therapy given via a vaginal
route (cream, ring, etc). Therefore, the
group using HT included the women
using vaginal HT plus women using
other forms of HT. The vaginal HT
group included women already using
vaginal HTupon entry into the study and
women who initiated vaginal HT at the
time of pessary initiation.
Prior to pessary tting, study patients
had a clean, plastic speculum inserted,
and vaginal secretion swabs were
collected on 2 sterile cotton tip swabs,
with care taken to sample from the
middle third of the vagina. One swab was
used to perform BV BLUE testing

729.e2 American Journal of Obstetrics & Gynecology NOVEMBER 2015

(OSOM Rapid Tests; Sekisui Diagnostics, Lexington, MA) at the time of the
visit.8 If the patient was found positive
for BV by BV BLUE at this baseline visit,
she was treated with 500 mg of oral
metronidazole twice daily for 7 days. If
the patient had an allergy to this medication, the patient was prescribed 300
mg of oral clindamycin twice daily for
7 days.
The second vaginal secretion swab was
rolled onto a dry, clean glass microscope
slide, air dried without a coverslip, and
transported to the laboratory and stored
at room temperature until the time of
Gram staining. After Gram staining,
Nugents criteria was used to dene the
presence of BV9 and allowed the laboratory assessor of the Gram stain to be
remote from the clinical study site and
unaware of the patients treatment
allocation.
Following the completion of vaginal
specimen collection and questionnaires,
patients were tted with a pessary that
was comfortable and allowed them to
adequately void. At the time of pessary
tting, patients were randomized to
either proceed with standard pessary
hygiene plus the use of TrimoSan gel
(half applicator of gel vaginally twice a
week) or to standard pessary care
without the use of TrimoSan gel.
The randomization scheme was a
blocked randomization sequence with
randomly alternating block size (block
size ranging from 5 to 10) with a 1:1 ratio
of TrimoSan gel to no TrimoSan gel,
stratied by women who intended to
remove their pessary at least daily and
women who intended to remove their
pessary less often than daily. The
randomization sequence was prepared
by a statistician uninvolved in patient
recruitment or allocation and was placed
in sequentially numbered opaque sealed
envelopes for the 2 different strata by an
investigator who also had no involvement in patient recruitment or treatment allocation.
Women stated their intention for
pessary removal frequency to the
research staff performing the randomization during their pessary tting, and
the investigator opened the next
sequentially numbered opaque sealed

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envelope in the appropriate strata to
assign the patients randomization group.
Patients randomized to the TrimoSan
group were then given TrimoSan gel and
instructions for its use, and patients
allocated to the control group were specically instructed not to use TrimoSan
gel. Patients were not blinded to their
treatment allocation.
Women were seen at 2 weeks and
3 months later for examination and
completed repeat questionnaires on pessary use, hygiene practices, and vaginal
symptoms, including additional questions regarding increase in the 4 vaginal
symptoms of discharge, itching, pain, and
sores since pessary tting. Women were
asked how often they removed their pessary (daily or more often, less often than
daily but at least once per week, less often
than once per week) and how often they
wore their pessary (never wear, wear 1-7
days per month, >7 days per month,
daily). They were also asked to rank their
desire to continue their pessary by a 5
point Likert scale. At each examination, a
midvaginal secretion swab was done to
perform the BV BLUE test in the clinic
and to prepare the microscopy slide for
Gram staining.
For the analysis of how frequently
women removed their pessary, frequent
pessary removal was dened as daily or
more often, whereas less often pessary
removal was dened as less often than
daily. Pessary satisfaction was dened as
a reply to the question, How much do
you want to keep wearing your pessary in
the future? Replies included quite a bit
or moderately. Excellent pessary satisfaction was dened as a reply of quite a
bit to this question.
We analyzed the prevalence of reported vaginal symptoms individually
and also for the presence of at least 1
reported vaginal symptom. We also
analyzed the prevalence of women
reporting an increase in 1 of 4 vaginal
symptoms since pessary tting (vaginal
discharge, itching, pain, sores) and the
prevalence of reporting an increase in at
least 1 of these 4 symptoms since pessary
tting.
The primary outcome was the rate of
BV by Gram stain (Nugents criteria) at 3
months after the pessary tting. The

Nugents score was determined by following a standardized Gram staining of

the microscope slide. BV was dened as a
Nugents score of 7 or greater, in accordance with Nugents criteria.9
Secondary outcomes included the rate
of BV at 2 weeks after pessary tting by
Nugents criteria, the rate of BV at 2
weeks and 3 months after pessary tting
by BV BLUE test, the prevalence of individual vaginal symptoms or at least 1
reported vaginal symptom at 2 weeks
and 3 months following pessary tting,
and the prevalence of the patient
reporting an increase in at least 1 of the 4
key vaginal symptoms (discharge, itching, pain, sores) since pessary tting at 2
weeks or 3 months.
We performed analyses both by
intention-to-treat (primary analysis) and
by per-protocol analysis. Women were
asked to report their frequency of TrimoSan use at each follow-up visit.
Women who used TrimoSan gel at least
once weekly were considered compliant
with TrimoSan use. The per-protocol
analysis was performed by comparing
those women who were compliant with
TrimoSan gel at least once a week (half
of the recommended dosing) to those
women who used the gel less frequently
or did not use the gel. Power calculation
was performed based on a 30% reported
prevalence of BV in pessary wearers, in
contrast to a prevalence of 10% in the
general population.6
For the primary outcome of BV as
detected by Gram stain 3 months after
pessary tting, the study sought to achieve a power of 88% at an a of 0.05 to
detect a lowering of the prevalence of BV
at 3 months in the TrimoSan-using
group from 30% back to the baseline
rate of 10%. This translated to a sample
size of 62 in each group. To account for at
least a 15% dropout rate after randomization, we planned to enroll 75 women
in each group. After initial recruitment
in the rst study site yielded a lower
follow-up rate than expected, the sample
size was expanded to 180 patients so that
a 70% rate of follow-up at 3 months
would achieve the predetermined power.
The effect of dichotomous variables
(such as randomization to TrimoSan,
any HTuse, vaginal HTuse, and frequent

pessary removal) on dichotomous outcomes was determined by c2 tests (with

Fisher exact test used in which there were
signicantly less than the expected
number of data points), and the effect of
dichotomous variables on continuous
variables was determined by t tests. For
the nonparametric variables (such as
parity and number of vaginal deliveries),
the Wilcoxon rank-sum test was used to
compare between 2 groups.
We utilized the Mantel-Haenzel
method to test the interaction of
different frequencies of pessary wearing
and pessary removal (as stated by the
patient at follow-up) with the relationship between the use of TrimoSan gel and
dichotomous outcomes. We also used the
Mantel-Haenzel method to test the effect
of HT use or vaginal HT use on the relationship between the use of TrimoSan gel
and dichotomous outcomes. We used
general linear models to examine the effect of frequency of pessary removal and
HT on the relationship between TrimoSan gel use and continuous outcomes
(such as the total Nugents score).
We used a linear regression model to
determine what other patient characteristics had an impact on the relationship between frequent pessary removal
or HT and outcomes when signicant
ndings were present in the uncorrected
analysis. If certain patient characteristics
were found to have an impact on the
relationship, we repeated the analysis
with correction for this variable.
We utilized a c2 test to analyze
whether there were signicant differences in BV prevalence or vaginal
symptoms at 2 weeks or 3 months between different reported frequencies
pessary use or pessary removal, again
utilizing the Fisher exact test where more
appropriate. As noted above, we dened
frequent pessary removal as once-daily
removal or more often and analyzed
the effect of frequent removal by a c2 test
on the BV and vaginal symptom
outcomes.

R ESULTS
There were 466 women screened for
eligibility during the study period
(Figure), with 86 women excluded
because of study criteria, 85 women

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729.e3

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FIGURE

Participant flow diagram

This figure demonstrates the flow of participants through the randomized trial design.
Meriwether. TrimoSan gel does not affect bacterial vaginosis in new pessary users. Am J Obstet Gynecol 2015.

declining to participate, and 108 women

not presenting for pessary tting after
being screened. The remaining 187
women who consented for participation
were randomized, of which 3 additional
women were excluded after randomization for the inability to be tted with a
pessary at their initial visit and patient
declination to attempt another tting.
This left 184 active eligible participants,
92 randomized to TrimoSan use and 92
randomized to no TrimoSan use.
Patient characteristics are presented
in Table 1 and did not vary between the
2 groups at baseline. The mean age of
the patients was 58.6
16.4 years,
the mean body mass index (BMI) was
28.3
7.5 kg/m2, the median parity was

3, and the majority of the women were

white (57%), Hispanic (23%), or African
American (10%). The prevalence of BV
(by Nugents criteria or by BV BLUE
testing) and the total Nugents score were
similar between the groups at baseline.
There were no differences between the
groups in the number of women requiring pessary retting at 2 weeks or 3
months. The 2 groups also did not differ
in the frequency of wearing or removing
the pessary reported by the patients at 2
weeks or 3 months and did not differ in
the prevalence of any HT use or vaginal
HT use.
There were 160 women of 184 eligible
study patients (87%) who presented
for either 2-week or 3-month follow-up,

729.e4 American Journal of Obstetrics & Gynecology NOVEMBER 2015

with 147 (79%) women presenting at 3

months for follow-up and 133 of them
(72%) qualifying for the primary
outcome measure with an interpretable 3 month Gram stain. Women who
presented for some type of follow up
(n 160) were more likely to have had a
vaginal infection within the last year
(16% vs 6%, P .04) but were otherwise
similar in characteristics to the women
who never presented for a follow-up after the initial visit (n 24).
The prevalence of BV did not differ
signicantly between groups at 2 weeks
or 3 months (Table 2). Pessary satisfaction was not different between the
groups at 2 weeks or 3 months, and
excellent pessary satisfaction was also

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similar between the groups at both time
points (P > .05). Pessary satisfaction
was substantially lower at 3 months than
at 2 weeks in both groups and overall
(88% at 2 weeks vs 62% at 3 months,
P < .01). Individual and composite
vaginal symptoms also did not differ
between the groups at 2 weeks or 3
months, although the prevalence of at
least 1 reported vaginal symptom was
high (>30% in both groups at 2 weeks
and >40% in both groups at 3 months;
Table 2). Also, the prevalence of an increase in at least 1 vaginal symptom since
pessary tting was high (>30% in both
groups at 2 weeks and 3 months; Table 2)
but did not differ between the groups.
In the TrimoSan group presenting for
follow-up, 53 of 64 women (83%) were
compliant with TrimoSan use at 2 weeks,
and only 39 of 62 women (63%) were
compliant at 3 months. The per-protocol
analysis, in which the group of women
compliant with TrimoSan gel use once a
week or more were compared with
women who used the gel less often or did
not use the gel did not substantially
change the results.
The reported frequency of wearing the
pessary or removing the pessary did not
signicantly affect any of the relationships between the randomization to
TrimoSan gel use and BV or vaginal
symptoms at 2 weeks or 3 months (all P
> .05). Comparisons between women
with different frequencies of wearing or
removing the pessary did not impact the
prevalence of BV at 2 weeks or 3 months
or the presence of at least 1 reported
vaginal symptom at 2 weeks or 3 months
(all P > .05).
There were 34 of 136 women reporting pessary removal frequency (25%)
who reported frequent (at least once a
day) pessary removal. Women reporting
frequent pessary removal were younger
than women who removed their pessary
less often (53 years vs 63 years, P < .01).
These women also had a lower Charlson Comorbidity Index (0.03 vs 1.03,
P < .01), were less likely to have HT
prescribed at their tting visit (3% vs
20%, P .03), tended to have higher
levels of education (P .03 all-groups
comparison for education level), and were
more likely to be sexually active (85% vs

TABLE 1

Study patient characteristics in the TrimoSan gel and no TrimoSan gel

groups

Variable
Age, ya
BMI, kg/m

2a

TrimoSan, n (%) or
mean SDa or
median (variance)b
(n [ 92)

No TrimoSan, n (%)
or mean SDa or
median (variance)b Total patients
(n [ 92)
(n [ 184)

58
15

60
17

59
16

29
7.6

28
7.4

28
7.5

56 (61)

48 (52)

Race
White
African American

105 (57)

6 (7)

13 (14)

19 (10)

23 (25)

20 (22)

43 (23)

Asian

1 (1)

3 (3)

4 (2)

Other

5 (5)

8 (9)

13 (7)

Hispanic

Parity

Vaginal deliveries

3 (2.6)
b

2 (2.4)

Indication for pessary use

Prolapse

41 (44)

45 (49)

86 (47)

Urinary incontinence

35 (38)

30 (33)

65 (35)

Both prolapse and

urinary incontinence

13 (14)

10 (11)

23 (13)

8 (9)

6 (7)

14 (8)

26 (28)

28 (30)

54 (29)

Smoking
Current
Past
Charlson
Comorbidity Indexa

0.77
1.1

0.89
1.8

0.82
1.5

Insurance type
Private

36 (39)

38 (41)

74 (40)

Public

27 (29)

34 (37)

61 (33)

None

7 (8)

6 (7)

13 (7)

Graduate

25 (27)

28 (30)

53 (29)

College

37 (40)

29 (32)

66 (36)

High school

20 (22)

28 (30)

48 (26)

3 (3)

4 (4)

7 (4)

Sedentary work

16 (17)

16 (17)

32 (17)

Homemaker

18 (20)

18 (20)

36 (20)

Light labor

20 (22)

26 (28)

46 (25)

Heavy labor

8 (9)

5 (5)

13 (7)

26 (28)

19 (21)

45 (24)

Education level

Less than high

school diploma
Job activity level

Unemployed or retired

Meriwether. TrimoSan gel does not affect bacterial vaginosis in new pessary users. Am J Obstet Gynecol 2015.(continued)

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TABLE 1

Study patient characteristics in the TrimoSan gel and no TrimoSan gel

groups (continued)

Variable

TrimoSan, n (%) or
mean SDa or
median (variance)b
(n [ 92)

No TrimoSan, n (%)
or mean SDa or
median (variance)b Total patients
(n [ 92)
(n [ 184)

Prior pelvic surgery

41 (49)

39 (42)

80 (43)

9 (10)

4 (4)

13 (7)

10 (11)

7 (8)

17 (9)

Using HT at time
of recruitment

22 (24)

24 (26)

46 (25)

Vaginal HT at time
of recruitment

19 (21)

19 (21)

38 (21)

HT prescribed at time
of recruitment

13 (14)

14 (15)

27 (15)

Required refitting
at 2 wks

13 (14)

12 (13)

25 (14)

Required refitting
at 3 mo

15 (16)

12 (13)

27 (15)

23 (25)

15 (16)

38 (21)

Prior pessary use

Vaginal infection history
Vaginal infection
last 12 mo
HT

Pessary refitting

BV measures
BV by Nugents criteria
at baseline
Total Nugents score
at baselinea

4.5
2.0

4.8
2.4

4.6
2.2

BV by BV BLUE
at baseline

1 (1)

2 (2)

3 (2)

BMI, body mass index; BV, bacterial vaginosis; HT, hormone therapy.
a

Designates that the mean / standard deviation is reported for that value; b Designates that the median (variance) is
reported for that value.

Meriwether. TrimoSan gel does not affect bacterial vaginosis in new pessary users. Am J Obstet Gynecol 2015.

49%, P < .01) than women who removed

the pessary less often.
Women who removed their pessary
frequently during the study had a
decreased prevalence of BV by Nugents
criteria at their initial baseline visit (6% vs
30%, P < .01). In the logistic regression
model, only age signicantly affected the
relationship between frequent pessary
removal and BV at baseline. Correcting
for age did not remove the signicant
relationship between frequent pessary
removal and BV at baseline (corrected
P .03), although correcting for either
sexual activity at baseline (corrected

P .13) or HT prescribed at pessary

tting (corrected P .06) made this
relationship no longer signicant. Frequent pessary removal was not associated
with a signicant difference in BV prevalence at 2 weeks (32% frequent vs 20%
nonfrequent, P .24) or 3 months (29%
frequent vs 22% nonfrequent, P .44),
and the prevalence of individual or composite vaginal symptoms was similar between frequent and nonfrequent pessary
removal at 2 weeks and 3 months (all
P > .05).
There were 66 of 184 women (36%)
using any HT during the study, 38 (21%)

729.e6 American Journal of Obstetrics & Gynecology NOVEMBER 2015

of which reported using vaginal HT. Any

HT or vaginal HT did not signicantly
affect the analysis of the relationship between TrimoSan gel randomization and
the study outcomes. Women using any
HTwere older than women who were not
(67 vs 54 years, P < .01) and similar in
other patient characteristics. Women who
were using any HT at baseline were more
likely to have BV by Nugents criteria at
baseline (33% vs 18%, P .03), but
women on any HT and women without
any HT did not differ in BV at baseline
when correcting for age (corrected P .33).
Women on any HT had similar rates of
BVat 2 weeks (19% vs 24%, P .57) and
3 months (26% vs 21%, P .55)
compared with women not using HT.
Interestingly, women using any HT
were more likely to report too much
vaginal discharge at 2 weeks (31% vs 4%,
P < .01), report an increase of vaginal
sores at 2 weeks (19% vs 0%, P < .01),
and were less likely to be satised with
their pessary at 2 weeks (21% vs 37%,
P .02). Correcting for age, the relationship of any HT use to a reported
increase in vaginal sores (corrected
P .01) and to decreased satisfaction
(corrected P .03) remained signicant.
Women using vaginal HT were similar
in age to women not using vaginal HT (65
vs 60 years, P .33), but women using
vaginal HT at baseline had a higher BMI
(29 vs 24 kg/m2, P .04). Women using
vaginal HT had a similar rate of BV by
Nugents criteria at baseline (24% vs 43%,
P .29) compared with women not
using vaginal HT but had a decreased risk
of BV at 2 weeks (7% vs 50%, P .04). At
3 months, the rate of BV was again similar
between women using vaginal HT and
not using vaginal HT (19% vs 13%,
P .70). The decreased risk of BV at 2
weeks for women using vaginal HT did
not remain signicant when correcting
for age (corrected P .10) and BMI
(corrected P .24). Women using vaginal
HT had similar rates of vaginal symptoms
at 2 weeks and 3 months (all P > .05).
There were no signicant differences in
BV prevalence or vaginal symptoms between the women initiating vaginal HT at
the pessary tting and the women who
were already using vaginal HT prior to
entry in to the study (all P > .05).

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C OMMENT
In this randomized, controlled, multicenter trial, the use of TrimoSan gel in
the rst 3 months after the initiation of
pessary use did not decrease the prevalence of BV or other outcomes such as
bothersome vaginal symptoms or a
desire to continue pessary use. Our data
indicate that the presence of at least 1
vaginal symptom is prevalent in pessary
users (>30% just 2 weeks after pessary
tting and >40% at 3 months) but that
TrimoSan gel use does not decrease these
symptoms.
Most women have improvement in
pelvic oor function and many meet
their goals after pessary insertion.4,10,11
Unfortunately, no interventions or hygiene practices after pessary tting have
been shown in prospective, clinical trials
to improve pessary care and satisfaction.7 Our ndings are consistent with
those in a previous study indicating
that BV occurs in 30% of pessary users6;
BV was found in approximately 24% of
our patients. This trial clinically tests a
pessary hygiene intervention meant to
prevent adverse pessary outcomes. Unfortunately, we did not nd that TrimoSan gel has a substantial inuence on
BV or other relevant pessary outcomes
studied.
It appears that women using a pessary
cannot be protected from BV by acidication of the vagina in this manner.
One hypothesis is that women who
develop this issue are physiologically
different than women who do not, either
in their inherent microbiome characteristics or in their immunological
response to a vaginal foreign body. It is
possible that other patient-initiated interventions may affect the rate of BV in
this population.
Although this study did not yield
evidence that TrimoSan gel use signicantly affected womens vaginal symptoms, these data do indicate that other
behavioral factors may affect the prevalence of BV. We found an association
between a decreased prevalence of BV
before pessary use and frequent pessary
removal after the pessary was initiated.
This indicates that women who go on
to remove their pessary frequently are

TABLE 2

Comparison of outcomes between the TrimoSan gel and no TrimoSan gel

groups (intent-to-treat analysis)
TrimoSan
No TrimoSan
gel, n (%)
gel, n (%) or
or mean SDa mean SDa P value

Variable
BV by Nugents criteria
2 wks (n 106, 60 TrimoSan)

12 (20)

12 (26)

.46

3 mo (n 133, 62 TrimoSan)

15 (24)

16 (23)

.82

Total Nugents score

2 wks (n 106, 60 TrimoSan)a

4.5
2.1

4.7
2.3

.75

3 mo (n 133, 62 TrimoSan)a

4.7
2.3

4.6
2.3

.83

2 wks (n 116, 63 TrimoSan)

0 (0)

2 (4)

.12

3 mo (n 137, 67 TrimoSan)

2 (3)

0 (0)

.15

2 wks (n 86, 49 TrimoSan)

44 (90)

32 (86)

.64

3 mo (n 115, 57 TrimoSan)

36 (63)

35 (60)

.76

2 wks (n 86, 49 TrimoSan)

26 (53)

21 (57)

.73

3 mo (n 115, 57 TrimoSan)

23 (40)

27 (47)

.50

28 (44)

21 (45)

.98

Vaginal discharge (n 110, 63 TrimoSan) 14 (22)

BV by BV BLUE test

Pessary satisfaction

Excellent pessary satisfaction

Vaginal symptoms
2 wks
At least 1 vaginal symptom
reported (n 110, 63 TrimoSan)

10 (21)

.91

11 (18)

8 (17)

.82

Vaginal pain (n 109, 61 TrimoSan)

6 (10)

3 (6)

.50

Vaginal cuts/sores (n 55, 33 TrimoSan)

4 (12)

1 (5)

.34

15 (41)

9 (35)

.83

1 vaginal symptom reported

(n 147, 72 TrimoSan)

30 (42)

24 (32)

.30

Vaginal discharge (n 147, 72 TrimoSan)

17 (24)

12 (16)

.25

Vaginal itching (n 147, 71 TrimoSan)

8 (11)

12 (16)

.42

Vaginal pain (n 144, 71 TrimoSan)

6 (8)

6 (8)

.96

Vaginal cuts/sores (n 78, 41 TrimoSan)

4 (10)

3 (8)

.80

18 (43)

13 (33)

.41

Vaginal itching (n 108, 60 TrimoSan)

1 vaginal symptom reported as

increased since pessary fitting
(n 63, 37 TrimoSan)
3 mo

1 vaginal symptom reported as

increased since pessary fitting
(n 81, 42 TrimoSan)
TrimoSan; Milex Pessaries, Cooper Surgical, Trumbull, CT.
BV, bacterial vaginosis.
a

Designates that the mean / standard deviation is reported for that value.

Meriwether. TrimoSan gel does not affect bacterial vaginosis in new pessary users. Am J Obstet Gynecol 2015.

NOVEMBER 2015 American Journal of Obstetrics & Gynecology

729.e7

SGS Papers
inherently at less risk for BV than women
who do not based on certain patient
characteristics, like sexual activity and HT
use. Furthermore, correction for other
factors such as sexual activity and HT
prescribed at the pessary tting did
remove the signicance of this association. This implies that sexually active
women without vaginal atrophy are likely
to remove their pessary more frequently
during the rst months of use. However,
these women who remove their pessary
frequently do not have a decreased prevalence of BVor an improved prole of any
other vaginal symptoms.
Women may be removing their pessary frequently for any number of lifestyle reasons, including for sexual
activity, but it does not seem that these
hygiene measures translate into different
outcomes. Because there are insufcient
data to guide patients in this area,7 patients can be reassured that a removal
frequency of their choice does not seem
to put them at great risk for BVor vaginal
symptoms. However, although we are
not aware of any present interventional
trials investigating the optimal frequency
of pessary removal, this study was also
not designed or powered to investigate
this particular question.
Whereas these data demonstrated that
HT did not affect the relationship between TrimoSan use and the study outcomes, HT does appear to be a factor in
vaginal symptoms and pessary satisfaction. It is known that a postmenopausal
state increases vaginal pH, and prevalence of BV increases with increasing age
and further into the menopausal transition.12,13 In this study, women using HT
were more likely to report an increase in
vaginal sores and be less satised with
the pessary 2 weeks into use, even correcting for the patient age.
This was not seen in women using
vaginal HT. This may be due to the fact
that women using any form of HT probably represent a mostly postmenopausal
group with atrophic vaginal tissue, and
43% of the group using any HT was not
using HT vaginally. Nonvaginal HT may
not be adequate to protect the vaginal
tissue from ulceration in the setting of a
foreign body and prevent pessary dissatisfaction associated with this issue.

ajog.org
In this population, vaginal HT
appeared to be protective for BV at 2
weeks on the uncorrected analysis,
consistent with the principle that higher
estrogen levels increase glycogen production and decrease vaginal pH.14,15
However, this signicant relationship
was no longer seen when the analysis was
corrected for patient age, and we did not
observe a difference in BVat the 3 month
follow-up between women using and
not using vaginal HT. We also did not
note any signicant relationship of
vaginal HT to adverse symptoms or
pessary satisfaction.
As noted in the previous text, this
furthers the hypothesis that women who
develop BV with a pessary are inherently
different from women who do not and
that BV in pessary users cannot be
attributable solely to age and lack of estrogen. The lack of signicant protection
associated with vaginal HT in this study
may also be attributable to the fact that
our study was not powered for this
analysis or to the fact that the pessary
may mitigate the protection offered by
vaginal hormones.
Strengths of this trial include the
randomized, controlled design of adequate power to detect a difference in
BV. The population was representative of
most populations of women who use
pessaries and for a variety of indications,
making it generalizable to most populations seeking pessary care. The study
patients did have the rate of BV expected
at the trials design, similar to rates seen
in 1 prior study in a pessary population6
and is further evidence that adequate
power was attained to detect so a relationship between TrimoSan if such an
association existed.
We also performed stratication by the
intended frequency of pessary removal
with the intent to minimize bias that
might be caused by the variable and
veried in the analysis that actual patient
practice in pessary removal frequency did
not affect the relationship between our
intervention and our main outcomes.
Also, the trial outcomes included 2
different measures of BV, one that could
be performed by a blinded assessor and
one whose results were immediately
available in the clinical setting, making

729.e8 American Journal of Obstetrics & Gynecology NOVEMBER 2015

the results further applicable to most

pessary providers.
Lastly, important covariates for the
vaginal environment, such as pessary
removal frequency and HT use, were
collected and considered in the analysis.
There are several limitations to this
study. First, although the assessor of the
primary outcomes was blinded to the
patients allocation, there was no blinding of the patients and no placebo use in
this trial. Because any substance applied
to the vagina may also affect the vaginal
microbiome, there is no placebo substance that is truly known to be inactive
in this patient population. Given the lack
of literature to guide the selection of a
veritable placebo, we believed that a
comparison with no gel (rather than a
placebo gel) was the most appropriate.
Second, exposure to TrimoSan gel, or
the per-protocol analysis, was done by
patient report. If women were using TrimoSan less compliantly than reported,
the relationship between TrimoSan gel
use and the outcomes would be overstated in our data, which did not nd a
signicant difference in outcomes. Also,
because only 63% of patients (39 of 62)
used TrimoSan once a week at 3 months,
we cannot state whether TrimoSan may
be shown effective if more patients had
been compliant with gel use.
Third, although we reported and
analyzed the effect of HT on this trials
outcomes, we did not intervene on the
patients use of HT. Given that there is
limited evidence on the effect of estrogen
use on BV in this particular population,
the authors wanted to be able to investigate this exposure without it being
controlled. Whereas bias from this factor
should be minimized by our randomized
design and our analysis indicated no
signicant interactions from HT between TrimoSan gel and the study outcomes, we cannot rule out the fact that
this affects the trial results.
Fourth, although the BV BLUE test has
correlated well with Gram stain results in
past studies,16 BV BLUE has not been
tested in a pessary-using patient population and, as stated by the manufacturer, is
not validated in women using vaginal
medications or foreign bodies.8,17 Many
of the women in this study who had BV

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by Nugents criteria did not have an BV
BLUEepositive test, so we concur that
this test is likely not accurate in pessary
users, and women who had BV at the
initial visit would not have been treated if
they had a negative BV BLUE test at their
clinical visit. Although the groups had a
similar prevalence of baseline BV by
Nugents criteria, we cannot exclude that
this affected the results.
Lastly, we did not use any other clinical
measures of BV (such as Amsels criteria)
as outcomes measures in this trial to avoid
potential bias introduced by a nonblinded
clinician and therefore cannot extend
these results to BV prevalence as detected
by these other outcome measures. Also, as
noted in a recent cross-sectional study on
the microenvironment in pessary users,18
shifts that increase the Nugent score
in pessary users are not necessarily related to bothersome vaginal discharge, so
Nugents criteria may not be accurately
measuring the process that actually troubles this population.
Overall, this trial provides data that
TrimoSan gel does not affect the prevalence of BV in new pessary wearers and
also does not affect vaginal symptoms or
desire to continue pessary use. However,
these data indicate that other hygiene
measures besides TrimoSan, such as the
frequency of removing the pessary or
HT use, may play a role in pessary
outcomes and merit further investigation. Findings from this trial will aid
clinicians in the counseling and management of women newly tted with a
pessary.
-

ACKNOWLEDGMENTS
We extend thanks to Sekisui Chemical Co, Ltd,
which provided discounted BV BLUE test kits for
use in this study. We also thank Ms Joanna
Peterson, RN (MedStar Washington Hospital
Center) and the Pessary Clinic staff of the University of New Mexico, including Ms Marsha
Grey, Ms Martha Rode, Ms Laura Migliaccio,
and Ms Abigail Reese, for their help with this
study. This study was registered at ClinicalTrials.
gov with the identier of NCT01471457.

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